1. Field of the Invention
The present invention relates generally to the field of pharmaceuticals, and particularly to the various pharmaceutical compositions which are used in the preparation and administration of TAXOL.RTM. and its derivatives.
2. Description of the Prior Art
TAXOL.RTM. (paclitaxel) is one of a class of drugs called taxanes. These types of drugs promote polymerization of tubulin and stabilize the structure of intracellular microtubules. This process has the effect of inhibiting the normal dynamic reorganization of the microtubules that is necessary for interphase and mitotic functions. Paclitaxel may also potentiate the cytotoxic effects of radiation.
In December of 1992, the Food and Drug Administration (FDA) approved the natural form of paclitaxel for treatment of metastatic ovarian cancer after failure of first-line or subsequent chemotherapy, and the use of paclitaxel for the treatment of metastatic breast cancer received marketing approval in April of 1994. Although paclitaxel has shown to have effects of inhibiting the progression of cancer in some patients, it has proven to be somewhat difficult to prepare and administer. Usually applied to patients intravenously, TAXOL.RTM. is diluted in a suitable parenteral fluid since it is available only in a somewhat viscous solution. Its insolubility in water makes administration of the drug somewhat difficult.
Therefore, a number of different compositions have been proposed to be used as solvents for preparing TAXOL.RTM. for injection. For Example, U.S. Pat. No. 5,478,860 discloses a manufacturing process mixing TAXOL.RTM. with olive or sunflower-seed oil and polyethyleneglycol (PEG) into a microemulsion. In addition, European Patent No. 639,577 discloses a process of manufacturing the derivatives of TAXOL.RTM. having enhanced solubility in water by way of using phosphooxymethyl (POM) or methyltheomethyl (MTM). The PCT petitioned International Publication, WO-9318757, discloses a process which solves the solubility problem and enhances the pharmaceutical stability through the development of liposome-encapsulated TAXOL.RTM. as a drug delivery system (DDS).
Presently, the most common form of solvent for preparing a TAXOL.RTM. injection solution is a mixture of dehydrated ethanol and polyepoxilated castor oil. The stability of injection solutions prepared in this manner is limited, and the use of these solutions after prolonged storage may result in the neutralization of the TAXOL.RTM. or induced side effects to the patient due to the dissociation of the TAXOL.RTM. in solution.
Therefore, there is a current need for a pharmaceutical compound which is effective in the preparation of a TAXOL.RTM. injection solution which maintains the stability of the TAXOL.RTM. in solution during prolonged storage. This is done in an effort to produce an injection solution which when administered to patients reduces the side effects normally associated with a TAXOL.RTM. injection solution prepared using previous disclosed or conventional methods.
Accordingly, the principle object of the present invention is to provide a pharmaceutical compound which is used for the preparation of TAXOL.RTM. as an injection solution.
Another object of the present invention is to provide a pharmaceutical compound which significantly reduces the side effects normally associated with the use of conventional TAXOL.RTM. injection solutions.